Bottom Line:
Our data suggest that silica nanoparticles themselves do not directly affect the allergen-specific immune response after concurrent topical application of nanoparticles and allergen.However, when present in allergen-adsorbed agglomerates, silica nanoparticles led to a low IgG/IgE ratio, a key risk factor of human atopic allergies.We suggest that minimizing interactions between nanomaterials and allergens will increase the safety of nanomaterials applied to skin.

Background: The skin is a key route of human exposure to nanomaterials, which typically occurs simultaneously with exposure to other chemical and environmental allergen. However, little is known about the hazards of nanomaterial exposure via the skin, particularly when accompanied by exposure to other substances.

Results: Repeated topical treatment of both ears and the shaved upper back of NC/Nga mice, which are models for human atopic dermatitis (AD), with a mixture of mite extract and silica nanoparticles induced AD-like skin lesions. Measurements of ear thickness and histologic analyses revealed that cutaneous exposure to silica nanoparticles did not aggravate AD-like skin lesions. Instead, concurrent cutaneous exposure to mite allergens and silica nanoparticles resulted in the low-level production of allergen-specific IgGs, including both the Th2-related IgG1 and Th1-related IgG2a subtypes, with few changes in allergen-specific IgE concentrations and in Th1 and Th2 immune responses. In addition, these changes in immune responses increased the sensitivity to anaphylaxis. Low-level IgG production was induced when the mice were exposed to allergen-silica nanoparticle agglomerates but not when the mice exposed to nanoparticles applied separately from the allergen or to well-dispersed nanoparticles.

Conclusions: Our data suggest that silica nanoparticles themselves do not directly affect the allergen-specific immune response after concurrent topical application of nanoparticles and allergen. However, when present in allergen-adsorbed agglomerates, silica nanoparticles led to a low IgG/IgE ratio, a key risk factor of human atopic allergies. We suggest that minimizing interactions between nanomaterials and allergens will increase the safety of nanomaterials applied to skin.

Fig3: Induction of systemic immune responses by Dp + nSP30 agglomerates in PBS. a–c Plasma levels of Dp-specific (a) IgE, (b) IgG, and (c) IgG1 and IgG2a as analyzed by ELISA at 24 h after final topical treatment of NC/Nga mice with Dp alone or Dp + nSP30 in PBS. (D) Numbers of Dp-specific IFN-γ- and IL-4-producing splenocytes after re-stimulation with 100 μg mL−1 Dp, as determined by using ELISPOT assays specific for each cytokine. Data are given as means ± SEMs (n = 5–12). **P < 0.01 vs. Dp-alone group

Mentions:
To clarify the effect of topical Dp + nSP30 on cutaneous allergic sensitization, we evaluated the systemic immune responses 24 h after the final treatment. Although Dp-specific IgE levels were higher in both the Dp-alone group and the Dp + nSP30 group than in the PBS group, Dp-specific IgE levels did not differ significantly between the Dp-alone group and the Dp + nSP30 group (Fig. 3a). In contrast, the levels of Dp-specific total IgG and all evaluated IgG subtypes were significantly lower in the Dp + nSP30 group than in the Dp-alone group (Fig. 3b and c). In addition, we confirmed that nSP30 dose-dependently suppressed IgG production (Additional file 2). IgG subclass responses have been used to assess the type of immune response; IgG1 is known to indicate a Th2-type response, whereas IgG2a indicates a Th1 response [23]. Thus it is possible that skin exposure to Dp + nSP30 suppressed both the Th1 and the Th2 responses.Fig. 3

Fig3: Induction of systemic immune responses by Dp + nSP30 agglomerates in PBS. a–c Plasma levels of Dp-specific (a) IgE, (b) IgG, and (c) IgG1 and IgG2a as analyzed by ELISA at 24 h after final topical treatment of NC/Nga mice with Dp alone or Dp + nSP30 in PBS. (D) Numbers of Dp-specific IFN-γ- and IL-4-producing splenocytes after re-stimulation with 100 μg mL−1 Dp, as determined by using ELISPOT assays specific for each cytokine. Data are given as means ± SEMs (n = 5–12). **P < 0.01 vs. Dp-alone group

Mentions:
To clarify the effect of topical Dp + nSP30 on cutaneous allergic sensitization, we evaluated the systemic immune responses 24 h after the final treatment. Although Dp-specific IgE levels were higher in both the Dp-alone group and the Dp + nSP30 group than in the PBS group, Dp-specific IgE levels did not differ significantly between the Dp-alone group and the Dp + nSP30 group (Fig. 3a). In contrast, the levels of Dp-specific total IgG and all evaluated IgG subtypes were significantly lower in the Dp + nSP30 group than in the Dp-alone group (Fig. 3b and c). In addition, we confirmed that nSP30 dose-dependently suppressed IgG production (Additional file 2). IgG subclass responses have been used to assess the type of immune response; IgG1 is known to indicate a Th2-type response, whereas IgG2a indicates a Th1 response [23]. Thus it is possible that skin exposure to Dp + nSP30 suppressed both the Th1 and the Th2 responses.Fig. 3

Bottom Line:
Our data suggest that silica nanoparticles themselves do not directly affect the allergen-specific immune response after concurrent topical application of nanoparticles and allergen.However, when present in allergen-adsorbed agglomerates, silica nanoparticles led to a low IgG/IgE ratio, a key risk factor of human atopic allergies.We suggest that minimizing interactions between nanomaterials and allergens will increase the safety of nanomaterials applied to skin.

Background: The skin is a key route of human exposure to nanomaterials, which typically occurs simultaneously with exposure to other chemical and environmental allergen. However, little is known about the hazards of nanomaterial exposure via the skin, particularly when accompanied by exposure to other substances.

Results: Repeated topical treatment of both ears and the shaved upper back of NC/Nga mice, which are models for human atopic dermatitis (AD), with a mixture of mite extract and silica nanoparticles induced AD-like skin lesions. Measurements of ear thickness and histologic analyses revealed that cutaneous exposure to silica nanoparticles did not aggravate AD-like skin lesions. Instead, concurrent cutaneous exposure to mite allergens and silica nanoparticles resulted in the low-level production of allergen-specific IgGs, including both the Th2-related IgG1 and Th1-related IgG2a subtypes, with few changes in allergen-specific IgE concentrations and in Th1 and Th2 immune responses. In addition, these changes in immune responses increased the sensitivity to anaphylaxis. Low-level IgG production was induced when the mice were exposed to allergen-silica nanoparticle agglomerates but not when the mice exposed to nanoparticles applied separately from the allergen or to well-dispersed nanoparticles.

Conclusions: Our data suggest that silica nanoparticles themselves do not directly affect the allergen-specific immune response after concurrent topical application of nanoparticles and allergen. However, when present in allergen-adsorbed agglomerates, silica nanoparticles led to a low IgG/IgE ratio, a key risk factor of human atopic allergies. We suggest that minimizing interactions between nanomaterials and allergens will increase the safety of nanomaterials applied to skin.